Strongly reducing magnesium(0) complexes.

A complex of a metal in its zero oxidation state can be considered a stabilized, but highly reactive, form of a single metal atom. Such complexes are common for the more noble transition metals. Although rare examples are known for electronegative late-main-group p-block metals or semimetals1-6, it is a challenge to isolate early-main-group s-block metals in their zero oxidation state7-11. This is directly related to their very low electronegativity and strong tendency to oxidize. Here we present examples of zero-oxidation-state magnesium (that is, magnesium(0)) complexes that are stabilized by superbulky, monoanionic, ß-diketiminate ligands. Whereas the reactivity of an organomagnesium compound is typically defined by the nucleophilicity of its organic groups and the electrophilicity of Mg2+ cations, the Mg0 complexes reported here feature electron-rich Mg centres that are nucleophilic and strongly reducing. The latter property is exemplified by the ability to reduce Na+ to Na0. We also present a complex with a linear Mg3 core that formally could be described as a MgI-Mg0-MgI unit. Such multinuclear mixed-valence Mgn clusters are discussed as fleeting intermediates during the early stages of Grignard reagent formation. Their remarkably strong reducing power implies a rich reactivity and application as specialized reducing agents.

Home visits in the Danish High Risk and Resilience Study - VIA 7: assessment of the home environment of 508 7-year-old children born to parents diagnosed with schizophrenia or bipolar disorder.

OBJECTIVE: The home environment provided by the caregivers of a child is an influential single factor for development and well-being. We aimed to compare the quality of the home environment of children at familial high risk of schizophrenia or bipolar disorder with population-based controls. METHODS: Danish nationwide registers were used to retrieve a cohort of 522 7-year-old children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) or none of these diagnoses (N = 200). The home environment was assessed using the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory). RESULTS: The proportion of children living in home environments that were evaluated not to meet the needs of a 7-year-old child was significantly larger in the two familial high-risk groups. This was true for 21% of the children with familial predisposition for schizophrenia and 7% of children with familial disposition for bipolar disorder. CONCLUSION: Children born to parents diagnosed with schizophrenia and to a lesser extent bipolar disorder are at an increased risk of growing up in a home environment with an insufficient level of stimulation and support. Identifying families with inadequate home environments is a necessary step towards specialized help and support to at-risk families.

Gold complexes for focused-electron-beam-induced deposition.

Four gold complexes were tested as a precursor for focused-electron-beam-induced deposition: [ClAu(III)Me2]2, ClAu(I)(SMe2), ClAu(I)(PMe3), and MeAu(I)(PMe3). Complexes [ClAu(III)Me2]2 and MeAu(I)(PMe3) are volatile, have sufficient vapor pressure at room temperature for deposition experiments, and were found to yield deposits that contain gold (29-41 and 19-25 atom %, respectively). Electrons easily remove the Cl ligand from [ClAu(III)Me2]2, and predominantly both methyl ligands are incorporated into the deposit. Electrons remove at least one methyl group from MeAu(I)(PMe3). Complexes ClAu(I)(SMe2) and ClAu(I)(PMe3) are not suitable as a precursor. They dissociate in vacuum, and the only volatile components are Cl, SMe2, and PMe3, respectively.

Comparative clinical effects of hydromorphone and morphine: a meta-analysis.

We have conducted a meta-analysis of the clinical effects of morphine and hydromorphone to compare their benefit in analgesia. Embase and Medline were searched with an end-date of June 2009 for randomized, controlled trials or observational studies that addressed comparative analgesic and side-effects or particular side-effects. Two researchers independently identified included studies and extracted the data. Estimates of opioid effects were combined by using a random-effects model. Meta-analysis of eight studies suggested that hydromorphone (494 patients) provides slightly better (P=0.012) clinical analgesia than morphine (510 patients). The effect-size was small (Cohen's d=0.266) and disappeared when one study was removed, although the advantage of hydromorphone was more evident in studies of better quality (Jadad's rating). Side-effects were similar, for example, nausea (P=0.383, nine studies, 456 patients receiving hydromorphone and 460 morphine); vomiting (P=0.306, six studies, 246 patients receiving hydromorphone and 239 morphine); or itching (P=0.249, eight studies, 405 patients receiving hydromorphone, 410 morphine). This suggests some advantage of hydromorphone over morphine for analgesia. Additional potential clinical pharmacological advantages with regard to side-effects, such as safety in renal failure or during acute analgesia titration, are based on limited evidence and require substantiation by further studies.

Medication review of community-dwelling seniors using intensified home-care service.

UNLABELLED: Investigations on medication burden, falling, and inappropriate dosing in renal impairment have been obtained in patients living in nursing homes. Data from home-dwelling patients in intensified ambulatory care, especially from Germany are scant. MATERIAL AND METHOD: We evaluated patients daily visited by an ambulatory care service (Cohort 1, n = 102, median age 80 y) or had care given by relatives only (cohort 2, n = 101, median age 76 y) at baseline (V1), 6 (V2) and 12 months (V3). RESULTS: At V1 patients in Cohort 1 had 5 (median, range 3 - 15) and at V3 6 (3 - 17) medications. No differences could be observed between cohorts regarding number and pattern of medications. At V1, 30/102 patients of Cohort 1 had creatinine measured within the last 6 months, 13/30 patients had an eGFR < 50 ml/min. 6/34 medications which need dose-adjustment were unadjusted. Low surveillance of renal function and unadjusted dosing were also observed at other visits and also in Cohort 2. Within 1 year, 29/75 mobile patients in cohort 1 had a fall, 18/29 patients had a benzodiazepine prescribed regularly, whereas a benzodiazepine was prescribed in 6/46 patients which did not fall (chi2 p = 0.004). In Cohort 2, the number of falling patients was lower (19/84 mobile patients, p = 0.028). 11/19 patients had a benzodiazepine prescribed, in contrast to 5/65 patients which did not fall (chi2 p = 0.001). CONCLUSIONS: It needs to be elucidated whether a care service can contribute to medication safety in patients e.g. by reviewing medication charts and organizing for controls of ancillary laboratory values.

Dinitrogen complexation and reduction at low-valent calcium.

Here we report that attempted preparation of low-valent CaI complexes in the form of LCa-CaL (where L is a bulky ß-diketiminate ligand) under dinitrogen (N2) atmosphere led to isolation of LCa(N2)CaL, which was characterized crystallographically. The N2 2- anion in this complex reacted in most cases as a very potent two-electron donor. Therefore, LCa(N2)CaL acts as a synthon for the low-valent CaI complex LCa-CaL, which was the target of our studies. The N2 2- anion could also be protonated to diazene (N2H2) that disproportionated to hydrazine and N2 The role of Ca d orbitals for N2 activation is discussed.

Appropriate dosing in patients with impaired renal function on medical wards before and after an educational intervention.

CONTEXT: Whereas in larger hospitals individualized dose adjustment in renal insufficiency can be provided by expert systems and pharmacists, these options are often not available in smaller hospitals. AIMS: We evaluated whether one short educational session for the medical staff of internal wards of a community hospital, focusing on creatinine clearance and dosing in renal insufficiency, and providing a list of frequently used drugs and their dosing schedule does reduce the rate of patients with unadjusted doses. MATERIAL AND METHODS: In patients with a creatinine clearance < 60 ml/min, dosing schedules for 92 drugs were determined. After a 6-month observation period (Cohort 1), an educational intervention and the above mentioned list were delivered to the medical staff. This intervention was followed by a further 6-months observation period (Cohort 2). RESULTS: In Cohort 1, 55/85 patients (median age 79 y) had at least one initially inappropriately adjusted medication, and 47/85 remained so at discharge, whereas in Cohort 2 (median age 77 y), 28/85 patients had at least one initially inappropriately adjusted medication (p = 0.014 compared to Cohort 1) and 27/85 remained so at discharge (p = 0.05). In Cohort 1, 46.0% of all prescriptions with drugs which need dose adjustment (n = 220) were not adjusted. After the intervention (Cohort 2), 25.6% of all prescriptions (n = 176) followed an unadjusted dosage (p < 0.001). CONCLUSION: This intervention was on a "low key"-level, and no further support e.g. academic detailing was effected. Despite this, we found a considerable reduction in the number of inappropriate doses in patients with impaired renal function.

Osseointegration of dental implants in ectopic engineered bone in three different scaffold materials.

The in vivo regeneration of bone flaps might be an alternative to autogenous bone grafting. The first human case of mandibular reconstruction using the greater omentum as a bioreactor was reported in 2016. However, whether engineered bone will support the osseointegration of dental implants has not yet been investigated. In this study, bone tissue engineering was performed in the greater omentum of nine miniature pigs using bone morphogenetic protein 2, bone marrow aspirate, and three different scaffolds: hydroxyapatite, biphasic calcium phosphate (BCP), and titanium. After 8 weeks, two implants were placed in each scaffold; after another 8 weeks, the bone blocks were harvested for radiographic, histological, and histomorphometric analysis. All implants exhibited sufficient primary stability, and the success rate was 100%. The bone-to-implant contact ratios (BICs) were 38.2%, 68.5%, and 42.9%; the inter-thread bone densities were 29.4%, 64.9%, and 33.5%; and the peri-implant bone-scaffold densities were 56.4%, 87.6%, and 68.6% in the hydroxyapatite, BCP, and titanium groups, respectively. The BIC showed a strong correlation (r = 0.76) with the peri-implant bone-scaffold density. This study shows that de novo engineered bone leads to successful osseointegration and therefore may allow implant-based prosthodontic rehabilitation.

Limited and localized magmatism in the Central Atlantic Magmatic Province.

The Central Atlantic Magmatic Province (CAMP) is the most aerially extensive magmatic event in Earth's history, but many questions remain about its origin, volume, and distribution. Despite many observations of CAMP magmatism near Earth's surface, few constraints exist on CAMP intrusions at depth. Here we present detailed constraints on crustal and upper mantle structure from wide-angle seismic data across the Triassic South Georgia Rift that formed shortly before CAMP. Lower crustal magmatism is concentrated where synrift sedimentary fill is thickest and the crust is thinnest, suggesting that lithospheric thinning influenced the locus and volume of magmatism. The limited distribution of lower crustal intrusions implies modest total CAMP volumes of 85,000 to 169,000 km3 beneath the South Georgia Rift, consistent with moderately elevated mantle potential temperatures (<1500 °C). These results suggest that CAMP magmatism in the South Georgia Rift is caused by syn-rift decompression melting of a warm, enriched mantle.

Appropriateness and surveillance of medication in a cohort of diabetic patients on polypharmacy.

CONTEXT: It is assumed that with increasing polypharmacy, medication surveillance by the General Practitioner (GP) and adherence to the therapy regimen by the patient will both decline. AIM OF THE STUDY: We evaluated clinical and medication records taken from GP documentations in a cohort of 102 diabetic patients (48 f, 54 m, median age 70, range 39 - 81) with 3 or more chronic prescriptions. Patients were asked about their current medication and its tolerability by means of a structured telephone interview. RESULTS: 45% of the patients received up to 6 medications, 36% 7 - 9 and 19% > 10. The main comorbidity was hypertension (93%) and symptomatic CAD (39%). The use of established medications (beta-blockers and ACE inhibitors) for these comorbidities was appropriate. Although 76% were eligible for a statin therapy, only 51% actually took a statin, and 28% had a dose lower than the defined daily dose. 68% of the patients had no prescriptions other than those recorded in the GP documentation, but 8% of the total number of medicines taken by the patients were not recorded in the GP's database. 62% of patients took all the medication prescribed by the GP, while 7% of all medicines recorded in the GP's database were not taken by the patients. In 10% of cases, an incompatible medication (defined in accordance with a consented list) was taken by the patient. 81% of patients regularly (twice per year) had their HbA1c checked, but only 62% had their potassium levels checked, despite the use of ACI and diuretics. Most patients knew the reason for taking at least one medication, but 18% knew this for less than half of their (multiple) medications. 70% of the patients said they had been informed about the possible risks of their medication by the GP, and 7% knew the risks for only one medication. CONCLUSION: In this cohort of patients on polypharmacy and with a high risk profile for adverse drug reactions, we found a mismatch between GPs' documentation of prescriptions and the medication taken by the patient. Patients had no detailed knowledge about indications and almost no knowledge about risks. Although the overall performance of therapy (appropriateness) was deemed sufficient, there would appear to be room for improvement in order to fill information gaps and strive for stricter surveillance.

Effects of selective COX-2 inhibition on prostanoids and platelet physiology in young healthy volunteers.

BACKGROUND: Selective inhibitors of cyclooxygenase-2 (COX-2) called coxibs, are effective anti-inflammatory and analgesic drugs. Recently, these drugs were associated with an increased risk for myocardial infarction and atherothrombotic events. The hypothesis of thromboxane-prostacyclin imbalance has been preferred to explain these unwanted effects. METHODS: We studied the effects of 14 days intake of rofecoxib (25 mg q.d.), celecoxib (200 mg b.i.d.), naproxen (500 mg b.i.d.) and placebo in a randomized, blinded, placebo-controlled study in young healthy volunteers (median age 25-30 years, each group n = 10). We assessed prostanoid metabolite excretion (PGE-M, TXB(2), 6-keto-PGF(1alpha), 11-dehydro-TXB(2), 2,3-dinor-TXB(2), and dinor-6-keto-PGF(1alpha)), the expression of platelet activation markers (CD62P, PAC-1, fibrinogen), platelet-leukocyte formation, the endogenous thrombin potential, platelet cAMP content and plasma thrombomodulin level. RESULTS: Naproxen suppressed biosynthesis of PGE-M, prostacyclin metabolites and thromboxane metabolites and thrombomodulin levels. In contrast, both coxibs had an inhibitory effect only on PGE-M, 6-keto-PGF(1alpha), and on dinor-6-keto-PGF(1alpha), whereas TXB(2), 2,3-dinor-TXB(2) and 11-dehydro-TXB(2) excretion were unaffected. None of the coxibs exerted significant effects on the expression of platelet activation markers, cAMP generation, platelet-leukocyte formation, or on thrombomodulin plasma levels. Interestingly, platelet TXB(2) release during aggregation was enhanced after coxib treatment following arachidonic acid or collagen stimulation. CONCLUSION: In young healthy volunteers coxibs inhibit systemic PGE(2) and PGI(2) synthesis. Platelet function and expression of platelet aggregation markers are not affected; however, coxibs can stimulate TXB(2) release from activated platelets. Combined decrease in vasodilatory PGE(2) and PGI(2) together with increased TXA(2) in proaggregatory conditions may contribute to coxib side effects.

Peripheral neuropathy in a child with Cree leukodystrophy.

The authors describe peripheral nerve involvement in a 12-month-old boy with Cree leukodystrophy. Nerve conduction and genetic studies were performed during investigation of his leukodystrophy. Mutation analysis of the eukaryotic initiation factor 2B5 gene detected homozygosity of the R195 mutation, confirming the diagnosis of Cree leukodystrophy. Median and posterior tibial motor nerve conduction study results were normal, but sensory responses in the median nerves were unobtainable bilaterally, in keeping with a sensory axonal neuropathy. Somatosensory-evoked potentials were absent in the upper extremities and delayed in the lower extremities, confirming sensory nerve involvement. This degree of sensory nerve involvement has not been previously reported in patients with eukaryotic initiation factor 2B5-related disorders. Peripheral neuropathy should be looked for both clinically and with electrodiagnostic studies in patients with eukaryotic initiation factor 2B-related disorders.

Monitoring effects of direct FXa-inhibitors with a new one-step prothrombinase-induced clotting time (PiCT) assay: comparative in vitro investigation with heparin, enoxaparin, fondaparinux and DX 9065a.

UNLABELLED: Selective, direct factor Xa-inhibitors are an emerging new class of antithrombotic drugs but their application in therapy may require adequate laboratory monitoring. A recently introduced assay for monitoring anti-FXa-activity using Russell's viper venom is based on the prothrombinase-induced clotting time (PiCT). In this study comparative data on the performance of PiCT using direct and indirect FXa-inhibitors and measurements of FXa-activity and aPTT are reported. METHODS: Whole citrated blood samples from six healthy volunteers were preincubated with UFH (0-1.0 IU/ml), enoxaparin (0-10 microg/ml), fondaparinux (0-1.0 microg/ ml) and DX 9065a (0-10 microg/ml). PTT, FXa-activity and PiCT in plasma were determined on an ACL coagulation analyzer. PiCT was done with both a 180-sec incubation period before recalcification (2-step), and without (1-step). FXa-activity was based on a chromogenic assay (S2222). RESULTS: FXa-activity was reduced 10-40% by the lowest concentration and by 80-95% by the highest concentration of all agents. At the highest concentration the maximum prolongation in aPTT exceeded 120 sec with UFH, enoxaparin and DX 9065a but was only marginally prolonged (increase 39 +/- 3 sec) by fondaparinux. Prolongation in PiCT was significantly different when the two PiCT-methods were compared e.g. at 1.0 IU/ml UFH, 137 +/- 25 (1-step) vs. 187 +/- 32 sec (2-step) (p < 0.001); at 10 microg/ml enoxaparin 83 +/- 9 sec vs. 130 +/- 15 (p < 0.001); at 1.0 microg/ml fondaparinux 48 +/- 5 sec vs. 73 +/- 9 sec (p < 0.001); at 10 microg/ml DX 9065a 28 +/- 3 vs. 25 +/- 2 (p < 0.01), respectively. The 2-step method was unable to detect a prolongation in the effects of DX 9065a, and at concentrations < 5 microg/ml clotting times were even shorter (e.g. 13 +/- 1 sec at 1.0 microg/ml DX 9065a) than the baseline readings (20 +/- 2 sec). CONCLUSIONS: Only the 1-step method (i.e. without pre-incubation) seems suitable for the monitoring of new, direct selective FXa-inhibitors.

Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects.

Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 µg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (P<0.05, family-wise error). Notably, there was a significant negative correlation between LSD-induced amygdala response to fearful stimuli and the LSD-induced subjective drug effects (P<0.05). These data suggest that acute administration of LSD modulates the engagement of brain regions that mediate emotional processing.

Pharmacokinetics and tolerability of a combination of indinavir, lopinavir and ritonavir in multiply pretreated HIV-1 infected adults.

OBJECTIVES: The authors evaluated the pharmacokinetics and tolerability of indinavir/lopinavir/ritonavir in a protease inhibitor only combination. METHODS: Plasma drug levels of patients taking indinavir/lopinavir/ritonavir 800/400/100mg twice daily (n = 24, group 1) were compared to patients taking either lopinavir/ritonavir 400/100mg (n = 35, group2) or indinavir/ritonavir 800/100mg (n = 33, group3) twice daily plus nucleos(t)ide reverse transcriptase inhibitors (NRTI). Steady-state drug concentrations were measured by LC/MS/MS. Minimum and maximum concentrations (C subsetmin, C subsetmax), area under the concentration-time curve (AUC subset0-12h), total clearance (CL subsettot) and half-life (t1/2) were calculated. HIV viral load, CD4 cell count and adverse events causing early termination of therapy were correlated over a period of 48 weeks. RESULTS: Plasma levels of lopinavir/ritonavir were significantly enhanced when combined with indinavir compared to a regimen of lopinavir/ritonavir+NRTI: Mean lopinavir AUC subset(0-12h) 80,912 ng*h/mL vs. 60,548 ng*h/mL; C subsetmin 4,633 ng/mL vs. 3,258 ng/mL; C subsetmax 8,023 ng/mL vs. 6,710 ng/mL. Mean ritonavir AUC(0-12h) 6,907 ng*h/mL vs. 3,467 ng*h/mL; Cmin 220 ng/mL vs. 125 ng/mL; C subsetmax 1,059 ng/mL vs. 522 ng/mL. Indinavir levels were comparable for both indinavir containing regimen. A significantly smaller number of patients stopped indinavir/lopinavir/ritonavir therapy (group1: 16.7%) than indinavir/ritonavir + NRTI treatment (group3: 45.5%) due to adverse events. Virological failure was the main reason for early termination of treatment with indinavir/lopinavir/ ritonavir before week 48 (group1: 50%). CONCLUSIONS: indinavir/lopinavir/ritonavir 800/400/ 100mg twice daily represents a therapy option with an adequate safety but only short term efficacy for extensively pretreated patients.

Pharmacokinetics and pharmacodynamic effects of a new antibody glycoprotein IIb/IIIa inhibitor (YM337) in healthy subjects.

BACKGROUND: This study describes the first administration of YM337, the Fab fragment of a humanized monoclonal antibody against the fibrinogen GP IIb/IIIa receptor, in healthy male humans. METHODS AND RESULTS: Platelet aggregation (20 micromol/L ADP), platelet adhesion, fibrinogen binding, bleeding time, and YM337 concentrations in plasma were studied in substudy 1 after single boluses of 0.025, 0. 05, 0.1, 0.2, and 0.4 mg/kg YM337 and in substudy 2 after a bolus (0. 35 mg/kg) plus 6 hours of infusion at different dose levels of YM337 (0.5, 0.75, 1.0, 1.5 microg. kg(-1) x min(-1)), with abciximab as reference drug (n=5 or 6 subjects per group). After the 0.2-mg/kg and 0.4-mg/kg boluses, fibrinogen binding was reduced by >80% and bleeding time was prolonged to approximately 60 minutes. Bolus followed by infusion of 1.0 and 1.5 microg x kg(-1) x min(-1) YM337 maintained inhibition of platelet aggregation >80%. Aggregation and bleeding time returned to normal within 24 hours. A bolus of 0.25 mg/kg of abciximab followed by an infusion of 0.125 microg x kg(-1) x min(-1) showed effects similar to those observed with the 0.5- and 0. 75-microg x kg(-1) x min(-1) infusion of YM337. In 53 subjects exposed to YM337, 1 case of transient thrombocytopenia and 3 minor bleeding events occurred. No human anti-chimeric antibodies were detected 2 weeks and 2 months after administration. CONCLUSIONS: YM337 effectively inhibits IIb/IIIa-mediated platelet aggregation and adhesion in humans. The results of this phase 1 study will give rise to further clinical evaluation of YM337.

Detection of secondary genetic aberrations in follicle center cell derived lymphomas: assessment of the reliability of comparative genomic hybridization and standard chromosome analysis.

Secondary chromosomal aberrations in follicle center cell derived lymphomas (FCDL) usually involve gains and losses of genetic material and may be an important prognostic value. In the present study, we aimed to determine the power of comparative genomic hybridization (CGH) as compared to standard chromosome analysis (CA) to detect such secondary aberrations. The same lymph node cell suspensions prepared from 30 patients with FCDL were analyzed in parallel by CGH and CA based on R banding. In all, 73 discrepancies were found. Sixty-two imbalances were detected only by CA and 11 only by CGH. In cases with completely resolved karyotypes (n= 17), the median number of discrepancies between CGH and CA was one. However, when the karyotype was partially resolved (n = 12), the median was four (P < 0.01). Discrepant results were further studied by fluorescence in situ hybridization using locus-specific probes. These data confirm, that not only for the detection of balanced aberrations, but also for the detection of unbalanced aberrations in FCDL, standard chromosome analysis is still the 'gold standard'. In contrast, CGH is useful to detect chromosomal imbalances when no metaphases are found or no fresh material is available.

P-selectin (CD62p) and P-selectin glycoprotein ligand-1 (PSGL-1) polymorphisms: minor phenotypic differences in the formation of platelet-leukocyte aggregates and response to clopidogrel.

INTRODUCTION: Formation of platelet-leukocyte aggregates (PLA) via the CD62p-ligand PSGL-1 represents an important mechanism by which leukocytes contribute to thrombotic and inflammatory events. Deficient variants (namely the Thr715Pro-SNP for CD62p and a VNTR-polymorphism for PSGL-1) might affect PLA formation and probably the response to clopidogrel (which is known to reduce PLA-formation). METHODS: CD62p-expression, PLA-formation and the up-regulation of CD11b before (V1) and 24 hours after (V2) a loading dose of clopidogrel 225 mg were investigated in ten wild-type controls, ten heterozygote carriers of the Thr715Pro-allele and five carriers of the rare PSGL-1 B-allele (2 A/B and 3 B/B). RESULTS: CD62p-expression before application of clopidogrel and under clopidogrel treatment in Pro715-haplotype samples did not differ from that in wild-type subjects. The response to clopidogrel was similar in all subjects. Pro715-carriers exhibited a significantly lower percentage of monocytes with platelets attached prior to clopidogrel treatment (ADP: median 22 (1st-3rd quartile 20-23), TRAP: 27 (25 - 38)) compared to the wild-type (ADP: 37 (31-44), TRAP: 55 (37-63)). These differences were not present under clopidogrel, and CD11b-expression was significantly reduced in both groups (controls: median 150 (quartile range 121 - 230) to 113 (121 - 230), Pro715-carriers: 147 (139 - 221) to 126 (109 - 170); all values refer to mean fluorescence intensity). Statistical analysis was not done in the case of PSGL-1 B-allele carriers, but PLA-formation before and under clopidogrel was always at the bottom end of the range seen in the control group and the Pro715-carriers or even below this range. CONCLUSION: Minor phenotypic differences in the CD62p-PSGL-1 axis could be demonstrated in this study. Carriers of these polymorphisms showed a full response to clopidogrel comparable to that in control subjects.